A highly effective inhibitor of gastric acid secretion used in the therapy of stomach ulcers and Zollinger-Ellison syndrome. Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell.

After oral administration, the onset of the anti-secretory effect of omeprazole occurs within one hour and maximum effect occurring within two hours. At 24 hours, inhibition of secretion is approximately 50% of maximum and duration of inhibition lasts up to 72 hours. Although omeprazole has a very short plasma half-life, the anti-secretory effect lasts for a long time due to prolonged binding to parietal H+/K+ ATPase enzyme. When the drug has been discontinued, secretory activity will return to baseline over 3-5 days. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days. In studies involving more than 200 patients, serum gastrin levels increased during the first 1 to 2 weeks of once-daily administration of therapeutic doses of omeprazole in parallel with inhibition of acid secretion. Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date.

Mechanism of action

Omeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity.

Absorption

The delayed-release capsule are enteric-coated (as omeprazole is acid-labile) so the absorption of omprazole begins once the granules leave the stomach. Absorption is rapid. Peak plasma levels occur within 0.5 - 3.5 hours. The absolute bioavailability (compared with intravenous administration) of the delayed-release capsule is 30-40% at doses of 20 - 40 mg, due to presystemic metabolism. This value increases slightly when given repeatedly. Based on a relative bioavailability study, the AUC and Cmax of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively. Interestingly, when the 40 mg delayed release capsule is given with or without applesauce, it is bioequivalent. However, when the 20 mg delayed release capsule is given with the same conditions, it is not bioequivalent. When the same capsule is given to the elderly, bioavailability increases. Omeprazole was 76% bioavailable.

Volume of distribution

Not Available

Protein binding

95% bound to human plasma protein.

Metabolism

Hepatic. Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system. The two primary CYP isozymes involved are CYP2C19 and CYP3A4. Metabolism is stereoselective in which the S-isomer is converted to 5'O-desmethylomeprazole via CYP2C19. CYP3A4 converts the S-isomer to 3-hydroxyomeprazole. The R-isomer is converted to 5-hydroxyomeprazole by CYP2C19. CYP3A4 converts the R-isomer to any four different metabolites: 5-hydroxyomeprazole (5-OH OME), omeprazole sulfone (OME sulfone), 5'-O-desmethylomeprazole (5'-desmethyl OME), and 3-hydroxyomeprazole (3-OH OME).

Urinary excretion is a primary route of excretion of omeprazole metabolites. Little, if any unchanged drug was excreted in the urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recovered in the feces.

Nineteen healthy male volunteers received a single 40 omeprazole delayed-release capsule once daily for 8 days (Days 1-8), and a single 200 mg avanafil on Day 8. Twelve hour pharmacokinetics of omeprazole on Days 7 and 8 were compared. Co-administration with avanafil resulted in an approximate 5.9% increase in AUC0-inf and 8.6% increase in Cmax of omeprazole.

Proton pump inhibitors such as omeprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.

Omeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Clopidogrel prescribing information recommends avoiding concurrent use with omeprazole, due to the possibility that combined use may result in decreased clopidogrel effectiveness.

The strong CYP2C19 inhibitor, Omeprazole, may decrease the metabolism and clearance of Trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Omeprazole is initiated, discontinued or dose changed.